| First Author | Luo Q | Year | 2019 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 60 |
| Issue | 6 | Pages | 1928-1936 |
| PubMed ID | 31042800 | Mgi Jnum | J:276025 |
| Mgi Id | MGI:6304784 | Doi | 10.1167/iovs.18-26045 |
| Citation | Luo Q, et al. (2019) The Diurnal Rhythm of Insulin Receptor Substrate-1 (IRS-1) and Kir4.1 in Diabetes: Implications for a Clock Gene Bmal1. Invest Ophthalmol Vis Sci 60(6):1928-1936 |
| abstractText | Purpose: Diabetes leads to the downregulation of the retinal Kir4.1 channels and Muller cell dysfunction. The insulin receptor substrate-1 (IRS-1) is a critical regulator of insulin signaling in Muller cells. Circadian rhythms play an integral role in normal physiology; however, diabetes leads to a circadian dysrhythmia. We hypothesize that diabetes will result in a circadian dysrhythmia of IRS-1 and Kir4.1 and disturbed clock gene function will have a critical role in regulating Kir4.1 channels. Methods: We assessed a diurnal rhythm of retinal IRS-1 and Kir4.1 in db/db mice. The Kir4.1 function was evaluated using a whole-cell recording of Muller cells. The rat Muller cells (rMC-1) were used to undertake in vitro studies using a siRNA. Results: The IRS-1 exhibited a diurnal rhythm in control mice; however, with diabetes, this natural rhythm was lost. The Kir4.1 levels peaked and troughed at times similar to the IRS-1 rhythm. The IRS-1 silencing in the rMC-1 led to a decrease in Kir4.1 and BMAL1. The insulin treatment of retinal explants upregulated Kir4.1 possibly via upregulation of BMAL1 and phosphorylation of IRS-1 and Akt-1. Conclusions: Our studies highlight that IRS-1, by regulating BMAL1, is an important regulator of Kir4.1 in Muller cells and the dysfunctional signaling mediated by IRS-1 may be detrimental to Kir4.1. |
